Bacterial expression and purification of a heterodimeric adrenomedullin receptor extracellular domain complex using DsbC-assisted disulfide shuffling

► A heterodimeric AM receptor ECD complex was purified using novel folding methodology. ► The RAMP2 ECD was properly folded by co-expression with DsbC in E. coli trxB gor. ► Proper folding of an MBP-CLR ECD fusion protein was dependent on RAMP2 ECD. ► DsbC-assisted disulfide shuffling enhanced RAMP2-dependent CLR ECD folding in vitro. ► The recombinant MBP-CLR:RAMP2 ECD complex selectively bound AM.